Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)-combined regimen for allogeneic bone marrow transplantation in refractory acute myeloid leukemia

S. Takahashi, S. I. Okamoto, N. Shirafuji, K. Ikebuchi, K. Tani, M. Shimane, T. Matsudaira, S. Irie, T. Tsuruta, E. Matsuishi, H. Ogura, Y. Kouzai, H. Kodo, A. Tojo, N. Satoh, K. Ozawa, S. Asano

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Abstract

Recombinant human glycosylated G-CSF (rhG-CSF) may stimulate proliferation of myeloid leukemia cells and thereby increase their susceptibility to anti cancer agents. By in vitro colony assay, the rhG-CSF-responsive NFS-60 leukemic cell clones are more effectively killed by Ara C in the presence of rhG-CSF than in the absence of rhG-CSF, while the killing of the rhG-CSF-unresponsive HL-60 cell clones is unaffected by rhG-CSF. Leukemia cell colony forming units (L-CFU) derived from most AML patients demonstrate similar results to those of the NFS-60 cell clone when treated in vitro. Encouraged by these in vitro results, we used rhG-CSF as a component of a conditioning regimen for 15 relapsed AML patients who were receiving allogeneic BMT. The patients were conditioned with total body irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose of 5 μg/kg/day from 24 h before the beginning of TBI to the end of Ara C therapy. Proliferation of the leukemia cells in vivo in response to rhG-CSF was confirmed in 7 of 14 patients tested and the combined use of rhG-CSF had no additional adverse effects. After BMT, four patients died of non-leukemic causes and three patients had leukemic relapse: the other eight patients have remained disease-free for 200-1600 (median 417) days. The actuarial probabilities of relapse and disease free survival (DFS) at 4.4 years after BMT were 43.2% and 41.7%, respectively. These results suggest that the rhG-CSF-combined preparative regimen for BMT has potential benefit in prolonging the duration of remission after BMT and improving DFS rate in AML.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalBone Marrow Transplantation
Volume13
Issue number3
Publication statusPublished - 1994 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Takahashi, S., Okamoto, S. I., Shirafuji, N., Ikebuchi, K., Tani, K., Shimane, M., Matsudaira, T., Irie, S., Tsuruta, T., Matsuishi, E., Ogura, H., Kouzai, Y., Kodo, H., Tojo, A., Satoh, N., Ozawa, K., & Asano, S. (1994). Recombinant human glycosylated granulocyte colony-stimulating factor (rhG-CSF)-combined regimen for allogeneic bone marrow transplantation in refractory acute myeloid leukemia. Bone Marrow Transplantation, 13(3), 239-245.